Macromolecular agents composed of serum albumin or linear polymers have MRI contrast enhancement factors less than those predicted for rigid molecules of comparable size. MRI contrast agents based upon dendrimers obviate this deficiency. Terminal primary amines of dendrimers are modified with chelating agents that subsequently form Gd(III) complexes as developed in our laboratories. These reagents possess a molar relaxivity up to 6 times that of Gd(III)DTPA and better than twice that of other macromolecular agents. Excellent conventional MR imaging and 3D T-O-F MR angiograms have been obtained. Studies have been expanded to thoroughly explore the utility of these agents. Evaluation of these macromolecular chelate conjugated dendrimer based Gd(III) MR contrast agents based on the PAMAM or the DAB classes of dendrimers have revealed that these agents can be tuned for various applications by virtue of choosing generation size, core elements, conjugation with elements of polyethylene glycol, and by adjusting clearance rates with co-administration of lysine. To this end, use of the PAMAM based agents has demonstrated the ability to image tumor vasculature accurately at the 200 ?m scale. The DAB class of agents has remarkably selective properties wherein reverse contrast images of metastatic liver tumors could be imaged at as small a scale as 0.3 mm. The PAMAM agents have also been used to develop am imaging technique to complement gene therapy methodology and provide not only an accurate accounting of the pharmacokinetics of the nucleotide, but also to then to image the targeted tissues. Lastly, we have demonstrated that these agents can be selectively targeted, not only by conjugation to antibodies, but to other vectors to deliver exceptionally high levels of Gd(III) into disseminated intraperitoneal ovarian cancer tumor for treatment by neutron capture therapy. Complementary to the MR contrast agents, ESR spin-label agents have been prepared based upon dendrimers and are undergoing evaluation. We have found that the use of a properly prepared spin label dendrimer conjugate can effectively enhance the biological half-life of a small molecular weight radical and thus potentially permit a more convenient ESR imaging protocol to be created. In addition to these two types of imaging technology, protein based and dendrimer based CT contrast agents have also been prepared and are being evaluated in the appropriate model systems. The CT contrast agent based upon albumin conjugated to iopanoic acid continues to be evaluated in pre-clinical rodent and primate models for use in quantifying flow and dispersion of therapeutics being injected inter-cranially. This material is compared to a MRI albumin-based reagent and preparations are underway to prepare this iodine-based reagent for use in clinical trials. Use of dendrimers to prepare a completely synthetic, and hence a reproducible analog of the CT albumin reagent has been initiated. A novel water-soluble analog of iopanoic acid has been prepared for this purpose and has been conjugated to the G4 dendrimer. Characterization studies continue for this macromolecule to define the targeted products prior to any in vivo evaluation versus conventional low molecular weight CT contrast agents.